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Marcellin P.,Hopital Beaujon | Roberts S.K.,Alfred Hospital | Reddy K.R.,University of Pennsylvania | Harrison S.A.,U.S. Army | And 7 more authors.
Expert Opinion on Drug Safety | Year: 2012

Objective: This analysis examines the safety profile of standard-versus high-dose peginterferon alfa-2a. Methods: Data were pooled from five trials including HCV genotype 1-or 4-infected naive and treatment-experienced patients (n 2,940). Patients were randomized to receive peginterferon alfa-2a at 180 μg/week (standard-dose; n 1,672) or 360 μg/week (high-dose; n 1,268) plus ribavirin 1,000/1,200 mg/day for 12 weeks; after 12 weeks, all received standard dose. This safety analysis was restricted to the first 12 weeks. Results: In standard and high-dose groups, similar frequencies of serious adverse events (SAEs, 3.2 and 4.2%, respectively) and treatment discontinuations for safety reasons (2.8 and 2.9%) were reported. More patients reported weight decrease as an adverse event (AE) in the 360 μg/week group (7.7 vs. 3.3%). Significant (p < 0.05) independent predictors for discontinuation due to safety were older age, male gender, lower albumin and low neutrophil count, but not the starting dose of peginterferon alfa-2a. Although more laboratory abnormalities were reported in patients receiving high-dose peginterferon alfa-2a, this was not reflected in AEs or discontinuations, suggesting these are adequately managed by dose modification. Conclusions: High-dose peginterferon alfa-2a for 12 weeks does not significantly increase the incidence of SAEs or discontinuations for safety reasons, beyond that of a standard dose regimen. © Informa UK, Ltd.


Marcellin P.,University Paris Diderot | Cheinquer H.,Hospital Of Clinicas Of Porto Alegre | Curescu M.,Victor Babes University of Medicine and Pharmacy Timisoara | Dusheiko G.M.,University College London | And 11 more authors.
Hepatology | Year: 2012

The ability to predict which patients are most likely to achieve a sustained virologic response (SVR) with peginterferon/ribavirin would be useful in optimizing treatment for hepatitis C virus (HCV). The objective of this large international noninterventional cohort study was to investigate the predictive value (PV) of a virologic response (VR) by weeks 2, 4, and 12 of treatment on SVR. Treatment-naive HCV monoinfected patients (N = 7,163) age ≥18 years were prescribed peginterferon/ribavirin at the discretion of the treating physician according to country-specific requirements in accordance with the local label. The main outcome measure was the PV of a VR (HCV RNA <50 IU/mL) by weeks 2, 4, and 12 of treatment for SVR24 (HCV RNA <50 IU/mL after 24 weeks of untreated follow-up) by HCV genotype. The overall SVR24 rate was 49.4% (3,541/7,163; 95% confidence interval [CI]: 48.3-50.6%). SVR24 rates in patients with an HCV RNA titer <50 IU/mL by weeks 2, 4, and 12, respectively, were 66.2% (95% CI: 60.4-71.7%), 68.4% (95% CI: 65.7-71.0%), and 60.3% (95% CI: 58.5-62.1%) among genotype 1 patients; 82.0% (95% CI: 76.8-86.5%), 76.3% (95% CI: 73.3-79.1%), and 74.2% (95% CI: 71.3-76.9%) among genotype 2 patients; 67.3% (95% CI: 61.1-73.1%), 67.3% (95% CI: 64.2-70.3%), and 63.8% (95% CI: 61.0-66.6%) among genotype 3 patients; and 59.4% (95% CI: 40.6-76.3%), 63.3% (95% CI: 54.3-71.6%), and 54.3% (95% CI: 47.5-60.9%) among genotype 4 patients. The absence of a VR by week 12 had the highest negative PV across all genotypes. Conclusion: A VR by week 2 or 4 had the highest positive PV for SVR24 and differed according to HCV genotype. © 2012 American Association for the Study of Liver Diseases.


Desai A.P.,University of Chicago | Satoskar R.,Georgetown University | Appannagari A.,North Shore University Health System | Reddy K.G.,Center for Liver Diseases | And 4 more authors.
Journal of Clinical Gastroenterology | Year: 2014

BACKGROUND AND GOALS:: Our institution shifted the care of patients with chronic liver disease (CLD) from Internal Medicine faculty, house staff, and consulting hepatology service to a co-managed unit staffed by academic hospitalists and hepatologists. The effect of co-management between hospitalists and hepatologists on the care of patients hospitalized with complications of CLD such as spontaneous bacterial peritonitis (SBP) is unknown. STUDY:: A retrospective chart review of 56 adult patients admitted with CLD and SBP from July 1, 2004 to June 30, 2010 was performed. Adherence rates to current management guidelines were measured along with costs and outcomes of care. RESULTS:: Patients admitted under the 2 models of care were similar; however, they consistently underwent paracentesis within 24 hours (100% vs. 79%, P=0.013), had appropriate avoidance of fresh-frozen plasma use (75% vs. 43%, P=0.05), received albumin (97% vs. 65%, P=0.002), and were discharged on SBP prophylaxis (91% vs. 37%, P<0.001) under the co-managed model compared with the conventional model. Costs of care were similar between the 2 groups. We note a trend toward improved outcomes of care under the co-management model as measured by transfer rates to the intensive care unit, inpatient mortality, 30-day readmission, and mortality rates. CONCLUSIONS:: These results support co-management between hospitalists and hepatologists as a superior model of care for hospitalized patients with SBP. Furthermore, this study adds to the growing literature indicating that efforts are needed to improve the quality of care delivered to CLD patients. Copyright © 2013 by Lippincott Williams & Wilkins.


Baclig M.O.,Research and Biotechnology Division | Baclig M.O.,University of Santo Tomas of Philippines | Chan V.F.,University of Santo Tomas of Philippines | Ramos J.D.A.,University of Santo Tomas of Philippines | And 2 more authors.
International Journal of Molecular Epidemiology and Genetics | Year: 2010

The 5'untranslated region (5'UTR) is often targeted to detect major genotypes in hepatitis C virus (HCV) but its insufficient sequence variation limits its usefulness for differentiating HCV subtypes. Subtyping has important implications to epidemiologic studies, clinical management, and vaccine development. Analysis of the nucleotide sequence of variable regions such as the non-structural 5B (NS5B) is considered the reference method for identifying HCV subtypes. We evaluated the accuracy of subtyping of HCV genotype 1 (HCV-1) samples from the Philippines by 5'UTR sequencing as compared with the NS5B sequence. A total of 30 patients infected with HCV-1 previously confirmed by PCR-RFLP and clinically diagnosed with chronic hepatitis C were analyzed. Nucleotide sequencing of the 5'UTR showed that 15 (50%) were identified as 1a and 15 (50%) were identified as 1b. Sequence analysis of the NS5B revealed that 13 (43%) belonged to subtype 1a while 17 (57%) belonged to subtype 1b. The most predominant subtype was 1b by NS5B sequencing. The predictive value of 5'UTR sequencing to subtype 1a was 73% while for subtype 1b, predictive value was 87%. Overall concordance between 5'UTR and NS5B sequencing was 80%. NS5B sequence and phylogenetic analysis is still the reference method for identifying HCV-1a and 1b subtypes.


Younossi Z.M.,Center for Liver Diseases | Younossi Z.M.,Inova Fairfax HospitalVA | Stepanova M.,Center for Outcomes Research in Liver Diseases | Omata M.,Yamanashi Prefectural Hospital Organization | And 3 more authors.
Medicine (United States) | Year: 2016

The interferon (IFN)-free regimens for chronic hepatitis C (CHC) have high efficacy and superior health-related quality of life (HRQOL) in European/North American patients. The impact of these regimens on HRQOL of the Japanese CHC patients is not known. The Short Form-36 was administered before, during, and after treatment to CHC patients with genotype 1 treated with ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) for 12 weeks and genotype 2 treated with SOF + RBV for 12 weeks in clinical trials. The HRQOL data were analyzed with reference to treatment regimens and clinical factors. A total of 494 CHC patients were included (19% cirrhotic, 69% genotype 1, 52% treatment-naive; 153 received SOF + RBV, 170 received LDV/SOF + RBV, 171 received LDV/SOF). The sustained virologic response-12 rates for these regimens were 97%, 98%, and 100%, respectively. CHC patients treated with LDV/SOF, SOF + RBV, or LDV/SOF + RBV regimens had similar HRQOL scores at baseline. During treatment, more adverse events were experienced by those treated with RBV-containing regimens (46% vs 22%, P < 0.0001). The decrements in HRQOL were also significant in RBV groups: up to -3.8 points (treatment week-4), -5.2 (treatment week-12), and -3.2 (posttreatment week-12) (all P < 0.001). In contrast, RBV-free regimen (LDV/SOF) was associated with an improvement in HRQOL up to +4.1 points throughout the treatment (P < 0.01). In multivariate analysis, the use of RBV was independently associated with lower HRQOL during and after treatment (beta up to -6.4 points, P = 0.0001). Japanese CHC patients treated with RBV-containing regimens show mild HRQOL impairment. In contrast, patients treated with LDV/SOF not only showed high efficacy but also improvement of HRQOL. Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved.


Iavarone M.,Center for Liver Diseases | Sangiovanni A.,Center for Liver Diseases | Massironi S.,Maggiore Hospital | Fraquelli M.,Maggiore Hospital | And 4 more authors.
Hepatology | Year: 2010

Dynamic contrast imaging techniques are considered the standard of care for the radiological diagnosis of hepatocellular carcinoma (HCC) in cirrhosis. However, the accuracy of radiological diagnosis depends largely on the degree of arterial hypervascularization, which increases with tumor size. Owing to the interplay and prognostic relevance of tumor vascularization and cell differentation, we asked ourselves whether tumor grade also affects the outcome of radiological diagnosis. Sixty-two HCCs (47 of which measured 1-2 cm) were consecutively detected in 59 patients with compensated cirrhosis under surveillance with ultrasound and confirmed by way of echo-guided biopsy and concurrent investigations with contrast-enhanced ultrasound (CE-US), computed tomography (CT), and gadolinium magnetic resonance imaging (MRI). Tumor cell differentiation was evaluated using Edmondson-Steiner criteria in liver cores of 0.9-5.0 cm (median 1.6 cm). Eighteen (29%) HCCs were grade I (1.5 cm), 28 (45%) were grade II (1.5 cm), 16 (26%) were grade III (1.8 cm), and none were grade IV. Contrast wash-in and wash-out were concurrently demonstrated in 21 (34%) tumors by way of CE-US, including three (16%) grade I and 18 (41%) grade II-III (P = 0.08); in 32 (52%) tumors by way of CT, including three (16%) grade I and 29 (66%) grade II-III (P = 0.0006); and 28 (47%) tumors by way of MRI, including three grade I (16%) and 25 (57%) grade II-III (P = 0.01). Among 1- to 2-cm tumors, the radiological diagnosis was achieved in two of 16 grade I and 17of 31 grade II-III tumors (P = 0.006). Conclusion: Tumor grade, a relevant predictor of disease severity, influences the accuracy of dynamic contrast techniques in the diagnosis of HCC. © 2010 American Association for the Study of Liver Diseases.


Te H.S.,Center for Liver Diseases | Jensen D.M.,University of Chicago
Clinics in Liver Disease | Year: 2010

This article reviews the prevalence, disease burden, genotype distribution, and transmission patterns of hepatitis B virus (HBV) and hepatitis C virus in the 6 World Health Organization regions. The global epidemiology of hepatitis B and C demonstrates a predominantly declining prevalence of the diseases. Improvement in the control of hepatitis B has been largely achieved with implementation of a more universal HBV vaccine program, although a large gap still remains in the effort toward global prevention of hepatitis B. The transmission of hepatitis C has been greatly impacted by mandatory screening of blood donors in most countries in the world, although intravenous drug use continues to be a major source of infection. Public education regarding the risks of exposure to infected paraphernalia as well as household items such as razors is necessary in the continuing effort to curb this disease. © 2010 Elsevier Inc. All rights reserved.


Calderon R.M.,Mount Sinai Medical Center | Cubeddu L.X.,Mount Sinai Medical Center | Cubeddu L.X.,Nova Southeastern University | Goldberg R.B.,Diabetes Research Institute | Schiff E.R.,Center for Liver Diseases
Mayo Clinic Proceedings | Year: 2010

The beneficial role of statins in primary and secondary prevention of coronary heart disease has resulted in their frequent use in clinical practice. However, safety concerns, especially regarding hepatotoxicity, have driven multiple trials, which have demonstrated the low incidence of statin-related hepatic adverse effects. The most commonly reported hepatic adverse effect is the phenomenon known as transaminitis, in which liver enzyme levels are elevated in the absence of proven hepatotoxicity. This class effect is usually asymptomatic, reversible, and dose-related. However, the increasing incidence of chronic liver diseases, including nonalcoholic fatty liver disease and hepatitis C, has created a new challenge when initiating statin treatment in patients with high cardiovascular risk. These diseases result in abnormally high liver biochemistry values, discouraging statin use by clinicians, fostering treatment discontinuation, and leaving a large number of at-risk patients untreated. A PubMed/MEDLINE search of the literature regarding statin safety (January 1, 1994-December 31, 2008) was performed, using the following search terms: statin safety, statin-related hepatotoxicity, and chronic liver disease and statin use, as well as the specific names of different statins and different liver diseases. Relevant clinical trials, review articles, panel discussions, and guideline recommendations were selected. This review supports the use of statin treatment in patients with high cardiovascular risk whose elevated aminotransferase levels have no clinical relevance or are attributable to known stable chronic liver conditions. For each patient, the decision should be based on an individual assessment of risks and benefits. © 2010 Mayo Foundation for Medical Education and Research.


Obrien C.,University of Miami | Agresti N.,Center for Liver Diseases
Current Hepatitis Reports | Year: 2012

As a result of rapid advance medicinal chemistry, the time frame 2011-2012 has been an exciting one that has witnessed the release of the first direct acting antiviral agents (DAA). Multiple enzymatic and protein regions of the virus can serve as targets for these new drugs. One of the newest and most promising of these targets is the NS5A protein. The structure of this protein consists of three separate domains that are still under investigation as far as their function. Information, however, suggests that the NS5A acts within the context of a multi-protein complex. There has now been rapid and extensive the investigation of the use of a multitude of NS5A inhibitors from a variety of pharmaceutical companies. The activities and results of these various inhibitors in both preclinical as well as their clinical trials are examined during the course of this review.© 2012 Springer Science+Business Media, LLC.


Fabrizi F.,Maggiore Hospital | Fabrizi F.,Center for Liver Diseases | Martin P.,Center for Liver Diseases
Clinics in Liver Disease | Year: 2010

Liver disease is a significant cause of morbidity and mortality in patients receiving long-term dialysis. This article summarizes the most recent information on epidemiology, clinical significance, and management of infection by hepatitis B and C viruses in this population. © 2010 Elsevier Inc. All rights reserved.

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